engleski

Genetic analysis of hypertrophic cardiomyopathy in 2 Croatian families

Hypertrophic cardiomiopathy (HCM) is a genetically and clinically heterogeneous myocardial disease that in most cases familial and transmitted in a dominant fashion. More than 140 different mutations in 11 sarcomeric genes have been described to date. The most frequently affected gene codes beta-myosin heavy chain (MYH 7) (35-50%). Previous genotype-phenotype correlation studies have shown that mutations carry prognostic significance (R403Q, R719W and R719Q mutations were identified as highly malignant defects). We analysed MYH 7 in 14 patients (7 female and 7 male), members of 12 unrelated families, with HCM. The median age of patients at the time of diagnosis was 11, 2 years. In 8 patients dominant inheritance was strongly suggested on the base of family history. Mutation analysis of MYH 7 was carried out for exons 8, 9, 13, 15, 16, 19, 20 and 23. Thirty-nine known mutations (9 malignant including R403Q, R719W and R719Q) ; 36 substitutions, 2 deletions and 1 insertion were analysed. The mutations were detected using mutation specific restriction enzyme assays and oligonucleotide sequencing. No mutation has been found in the analysed patients. The non-existence of malignant mutation amongst the analysed patients, especially those with a positive family history, it difficult to explain on the basis of published studies till 2000. The research carried out by Ackerman in 2001, has shown for the first time very low incidence of malignant mutations, less than 1%, what also confirm results of this study.

hypertrophic cardiomyopathy; MYH 7; childhood

nije evidentirano